Alpha-2 (α2) receptors are adrenergic receptors; that is, they are receptor-targets of specific hormones (catecholamines), especially noradrenaline (norepinephrine) and adrenaline (epinephrine), that are released by the adrenal glands in response to stress.[1] Both subsystems are parts of the sympathetic nervous system. [edit] Effect The α2 receptor has several, general, functions in common with other α-receptors, but also has individual effects. [edit] General Common (or still unspecified) effects include: [edit] Individual Individual actions of the α2 receptor include: [edit] Mechanism The alpha subunit of an inhibitory G protein - Gi dissociated from the G protein, and associates with adenyl cyclase (also known as adenylate cyclase or adenylyl cyclase). This causes the inactivation of adenyl cyclase, resulting in a decrease of cAMP produced from ATP. This leads to a decrease of intracellular cAMP. Protein Kinase A is not able to be activated by cAMP, and so phosphorylase kinase cannot be phosphorylated by PKA. Phosphorylase kinase is responsible for the phosphorylation of proteins, and so there is a decrease in the levels of phosphorylated proteins, and the eventual cell response is decreased. The relaxation of gastrointestinal tract motility is by presynaptic inhibition[6], where transmitters inhibit further release by homotropic effects. [edit] Agonists Epinephrine has higher affinity for the alpha-2 receptor than has norepinephrine, which, in turn, has much higher affinity than has isoprenaline.[6] Other agonists include: - Nonselective
- α2A selective
- α2C selective
* denotes selective agonists to the receptor. Clonidine is an Alpha 2 Agonist used to reduce blood pressure. It was initially thought to act via presynaptic Alpha 2 receptors, reducing the amount of NE released. However, it binds to imidazoline receptors with a much greater affinity than Alpha 2 receptors. Imidazoline Receptors occur in the Nucleus Tractus Solitarii & Ventrolateral Medulla. Clonidine is now thought to decrease BP via this central mechanism. [edit] Antagonists (Alpha blockers) - Nonselective
- α2A selective
- α2B selective
- α2C selective
* denotes selective agonists to the receptor.
There are three types of α2 receptors in humans; ADRA2A, ADRA2B and ADRA2C. Some other species express a fourth α2D subtype also.[11] [edit] See also [edit] References - ^ University of California, San Diego, Health Library, catecholamines.
- ^ Goodman Gilman, Alfred. Goodman & Gilman's The Pharmacological Basis of Therapeutics. Tenth Edition. McGraw-Hill (2001): Page 140.
- ^ Woodman OL, Vatner SF (1987). "Coronary vasoconstriction mediated by α1- and α2-adrenoceptors in conscious dogs". Am. J. Physiol. 253 (2 Pt 2): H388–93. PMID 2887122. http://ajpheart.physiology.org/cgi/content/abstract/253/2/H388.
- ^ Elliott J (1997). "Alpha-adrenoceptors in equine digital veins: evidence for the presence of both α1 and α2-receptors mediating vasoconstriction". J. Vet. Pharmacol. Ther. 20 (4): 308–17. doi:10.1046/j.1365-2885.1997.00078.x. PMID 9280371.
- ^ Sagrada A, Fargeas MJ, Bueno L (1987). "Involvement of α1 and α2 adrenoceptors in the postlaparotomy intestinal motor disturbances in the rat". Gut 28 (8): 955–9. doi:10.1136/gut.28.8.955. PMID 2889649.
- ^ a b c d e f g Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 163
- ^ Wright EE, Simpson ER (1981). "Inhibition of the lipolytic action of beta-adrenergic agonists in human adipocytes by alpha-adrenergic agonists". J. Lipid Res. 22 (8): 1265–70. PMID 6119348. http://www.jlr.org/cgi/content/abstract/22/8/1265.
- ^ a b Fitzpatrick, David; Purves, Dale; Augustine, George (2004). "Table 20:2". Neuroscience (Third ed.). Sunderland, Mass: Sinauer. ISBN 0-87893-725-0.
- ^ Khan ZP, Ferguson CN, Jones RM (1999). "alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role". Anaesthesia 54 (2): 146–65. doi:10.1046/j.1365-2044.1999.00659.x. PMID 10215710.
- ^ online-medical-dictionary.org
- ^ Ruuskanen JO, Xhaard H, Marjamäki A, Salaneck E, Salminen T, Yan YL, Postlethwait JH, Johnson MS, Larhammar D, Scheinin M (January 2004). "Identification of duplicated fourth alpha2-adrenergic receptor subtype by cloning and mapping of five receptor genes in zebrafish". Molecular Biology and Evolution 21 (1): 14–28. doi:10.1093/molbev/msg224. PMID 12949138.
[edit] External links | Transmembrane receptor: G protein-coupled receptors | | | Class A: Rhodopsin like | | | | | | | | | | | | | | | GPR ( 1, 3, 4, 6, 12, 15, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 31, 32, 33, 34, 35, 37, 39, 42, 44, 45, 50, 52, 55, 61, 62, 63, 65, 68, 75, 77, 78, 82, 83, 84, 85, 87, 88, 92, 101, 103, 109A, 109B, 119, 120, 132, 135, 137B, 139, 141, 142, 146, 148, 149, 150, 151, 152, 153, 160, 161, 162, 171, 173, 174, 176, 177, 182) | | | | Adenosine ( A1, A2A, A2B, A3) · P2Y ( 1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14) | | | | | | | Other | Acetylcholine ( M1, M2, M3, M4, M5) · Adrenomedullin · Anaphylatoxin ( C3a, C5a) · Angiotensin ( 1, 2) · Apelin · Bile acid · Bombesin ( BRS3, GRPR, NMBR) · Bradykinin ( B1, B2) · Cannabinoid ( CB1, CB2) · Chemokine · Cholecystokinin ( A, B) · Dopamine ( D1, D2, D3, D4, D5) · EBI2 · Endothelin ( A, B) · Estrogen · Formyl peptide ( 1, 2, 3) · Free fatty acid ( 1, 2, 3, 4) · FSH · Galanin ( 1, 2, 3) · Gonadotropin-releasing hormone ( 1, 2) · GHB receptor · Ghrelin · Histamine ( H1, H2, H3, H4) · Kisspeptin · Luteinizing hormone/choriogonadotropin · lysophosphatidic acid ( 1, 2, 3) · Lysophospholipid ( 1, 2, 3, 4, 5, 6, 7, 8) · MAS ( 1, 1L, D, E, F, G, X1, X2, X3, X4) · Melanocortin ( 1, 2, 3, 4, 5) · MCHR ( 1, 2) · Melatonin ( 1A, 1B, 1C) · Niacin ( 1, 2) · Motilin · Opioid ( Delta, Kappa, Mu, Nociceptin & Zeta, but not Sigma) · Olfactory · Opsin ( 3, 4, 5, 1LW, 1MW, 1SW, RGR, RRH) · Orexin ( 1, 2) · Oxytocin · Oxoglutarate · PAF · Prokineticin ( 1, 2) · Prolactin-releasing peptide · Protease-activated ( 1, 2, 3, 4) · Relaxin ( 1, 2, 3, 4) · Somatostatin ( 1, 2, 3, 4, 5) · Sphingosine-1-phosphate ( 1, 2, 3, 4, 5) · SREB · Succinate · TAAR ( 1, 2, 3, 5, 6, 8, 9) · Tachykinin ( 1, 2, 3) · Thyrotropin · Thyrotropin-releasing hormone · Urotensin-II · Vasopressin ( 1A, 1B, 2) | | | | Class B: Secretin like | | | GPR ( 56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 157) | | | Other | Brain-specific angiogenesis inhibitor ( 1, 2, 3) · Cadherin ( 1, 2, 3) · Calcitonin · CALCRL · CD97 · Corticotropin-releasing hormone ( 1, 2) · EMR ( 1, 2, 3) · Glucagon ( GR, GIPR, GLP1R, GLP2R) · Growth hormone releasing hormone · PACAPR1 · GPR · Latrophilin ( 1, 2, 3, ELTD1) · Methuselah-like proteins · Parathyroid hormone ( 1, 2) · Secretin · Vasoactive intestinal peptide ( 1, 2) | | | Class C: Metabotropic
glutamate / pheromone | | | TAS1R ( 1, 2, 3) · TAS2R ( 1, 3, 4, 5, 8, 9, 10, 12, 13, 14, 16, 38, 39, 40, 41, 43, 44, 45, 46, 47, 48, 49, 50) | | | Other | Calcium-sensing receptor · GABA B ( 1, 2) · Glutamate receptor ( Metabotropic glutamate ( 1, 2, 3, 4, 5, 6, 7, 8)) · GPRC6A · GPR ( 156, 158, 179) · RAIG ( 1, 2, 3, 4) | | | | Frizzled / Smoothened | | | |
